Inhalant abuse is a significant, worldwide public health problem, yet there is a paucity of research on this issue, particularly research on the psychopharmacology of inhalants in humans We have developed a human laboratory model of inhalant abuse by studying the reinforcing, subjective, and cognitive/psychomotor effects of inhaled anesthetics in healthy humans who report no history of drug dependence A common finding in our studies is the observation of individual differences in subjective effects of inhalants, variability that is important in our current model but which is not desirable in some research issues we want to address, such as the mechanisms responsible for inhalant effects that are specifically associated with inhalant abuse It is imperative in such research to select subjects who are capable of reporting a profile of effects predictive of inhalant abuse We could accomplish that goal by studying inhalant abusers, however, there are practical and ethical issues that discourage this solution Instead, we have chosen to utilize a pre-screening procedure that has been shown to identify non-drug abusers who consistently and reliably report subjective effects that are associated with drug abuse (Busto et al, 1999) Subjects who report such subjective effects in response to the inhalants we test (nitrous oxide [N2O] and volatile anesthetics) will serve as surrogates for inhalant abusers in our laboratory model There are two specific aims of the proposed research:1) to establish the reliability and validity of the pre-screening procedure for use with inhaled anesthetics, and 2) to establish that inhalant Responders (subjects who report a profile of subjective effects indicative of inhalant abuse), as identified by the pre-screening procedure, are ideal surrogate subjects for inhalant abuse liability studies (that is, they respond as we would predict inhalant abusers would respond) The use of surrogate subjects will enhance our understanding of inhalant abuse by enabling the safe, ethical, and efficient study of inhalant effects associated with inhalant abuse in humans, thus bridging the gap between pre-clinical studies and epidemiological/treatment research. [unreadable] [unreadable]